NCT00932971

Brief Summary

Randomized, double blind study comparing the efficacy of pegylated interferon-alfa2a plus placebo versus pegylated interferon-alfa2a plus tenofovir for the treatment of chronic delta hepatitis. 70 Patients will be randomized 1:1 into the two groups. Treatment duration: 96 weeks. Follow-up: 24 weeks. Long-term-follow-up: until week 358.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
70

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Jun 2009

Longer than P75 for phase_2

Geographic Reach
3 countries

10 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2009

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

July 3, 2009

Completed
4 days until next milestone

First Posted

Study publicly available on registry

July 7, 2009

Completed
8.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2017

Completed
1 day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 2, 2017

Completed
Last Updated

January 29, 2018

Status Verified

January 1, 2018

Enrollment Period

8.2 years

First QC Date

July 3, 2009

Last Update Submit

January 26, 2018

Conditions

Hepatitis D

Outcome Measures

Primary Outcomes (1)

  • Negativation of HDV-RNA at the end of therapy

    week 96

Secondary Outcomes (11)

  • Negativation of HDV-RNA at week 48 of treatment

    week 48

  • Negativation of HDV-RNA 24 weeks after the end of treatment

    week 120

  • Normalization of ALT levels at the end of treatment and at the end of follow-up

    week 96 and week 356

  • HDV-RNA-levels over time

    up to week 356

  • Suppression of HBV-DNA below 6 IU/ml using the Cobas TaqMan assay at treatment weeks 48 and 96 and 24 weeks after treatment

    week 48, week 96, week 120

  • +6 more secondary outcomes

Study Arms (2)

PEG-IFN alfa-2a plus placebo

PLACEBO COMPARATOR

Pegylated interferon alfa-2a 180 µg once weekly (QW) subcutaneous (sc) plus placebo once daily, orally

Drug: PEG-IFN alfa-2a, placebo

PEG-IFN alfa-2a plus Tenofovir

ACTIVE COMPARATOR

Pegylated interferon alfa-2a 180 µg once weekly (QW) subcutaneous (sc) plus Tenofovir disoproxilfumarat 245mg once daily, orally

Drug: PEG-IFN alfa-2a, Tenofovir

Interventions

PEG-IFN alfa-2a, TenofovirDRUG

Pegylated interferon alfa-2a, 180µg once weekly, subcutaneously; Tenofovir disoproxilfumarat, 245mg, once daily, orally

Also known as: Pegasys, Viread
PEG-IFN alfa-2a plus Tenofovir
PEG-IFN alfa-2a, placeboDRUG

Pegylated interferon alfa-2a, 180µg once weekly, subcutaneously; Placebo, once daily, orally

Also known as: Pegasys
PEG-IFN alfa-2a plus placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Written informed consent.
  • Age \> 18 years.
  • Positive HBsAg, for at least the prior 6 months, positive anti-HDV for at least 3 months and positive for HDV-RNA by PCR within the screening period.
  • Elevated serum ALT ≥ ULN but ≤ 10X ULN as determined by two abnormal values taken \> 1 month apart during the 12 months before the first dose of study drug with at least one of the determinations obtained ≤ 35 days prior to the first dose.
  • A liver biopsy obtained within the past 12 months demonstrating liver disease consistent with chronic hepatitis. Patients with cirrhosis on liver biopsy must also have a liver imaging investigation to rule out hepatic carcinoma.
  • Negative urine or serum pregnancy test documented within the 24 hour period prior to the first dose of test drug.
  • Additionally, all fertile males with partners of childbearing age and females should use two reliable forms of effective contraception (combined) throughout the entire period of the study (treatment and for 4 months after treatment completion)
  • Creatinine clearance ≥ 70 mL/min

You may not qualify if:

  • Patients must not have received antiviral therapy for their chronic hepatitis D within the previous 6 months. Patients who are expected to need systemic antiviral therapy other than that provided by the study at any time during their participation in the study are also excluded.
  • Positive test at screening for HAV-Ag-IgM, HCV-RNA or HCV-Ag or HIV-Ag.
  • Serum concentrations of ceruloplasmin or alpha-1-antitrypsin consistent with an increased risk of metabolic liver disease.
  • Evidence of decompensated liver disease (Childs B-C).
  • History or other evidence of a medical condition associated with chronic liver disease (e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposures, thalassemia).
  • Women with ongoing pregnancy or who are breast feeding.
  • WBC count of \< 3.000 cells/ mm3; neutrophil count \< 1.500 cells/mm3or platelet count \< 90.000 cells/mm3.
  • Evidence of alcohol and/or drug abuse within one year of entry.
  • Patients are excluded if any history of psychiatric disease, especially depression, or of suicidal attempts is evident.
  • History of immunologically mediated disease.
  • History or other evidence of decompensated liver disease.
  • History or other evidence of chronic pulmonary disease associated with functional limitation.
  • History of severe cardiac disease
  • Evidence of an active or suspected cancer or a history of malignancy where there is a risk of cancer to recur.
  • History of having received any systemic anti-neoplastic (including radiation) or immunomodulatory treatment (including systemic corticosteroids) ≤ 6 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study.
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

Charité Campus Virchow-Klinikum, Med. Klinik für Gastroenterologie und Hepatologie

Berlin, 13353, Germany

Location

Friedrich-Wilhelms-Universität, Med. Klinik und Poliklinik I

Bonn, 53105, Germany

Location

Universitätsklinikum Düsseldorf, Klinik für Gastroenterologie

Düsseldorf, 40225, Germany

Location

Klinikum der J.W. Goethe-Universität

Frankfurt, 60590, Germany

Location

Universitätsklinikum Hamburg-Eppendorf, Klinik für Innere Medizin

Hamburg, 20246, Germany

Location

Medizinische Hochschule Hannover, Zentrum Innere Medizin

Hanover, 30625, Germany

Location

Medizinische Fakultät der Universität Heidelberg, Innere Medizin IV

Heidelberg, 69120, Germany

Location

Athens University School of Medicine, Hippokration General Hospital

Athens, 11527, Greece

Location

Institutul de Boli Infectioase "Prof. Dr. Matei Bals"

Bucharest, 021105, Romania

Location

Spitalul Clinic de Boli Infectioase si

Timișoara, 300312, Romania

Location

Related Publications (8)

  • Heidrich B, Deterding K, Tillmann HL, Raupach R, Manns MP, Wedemeyer H. Virological and clinical characteristics of delta hepatitis in Central Europe. J Viral Hepat. 2009 Dec;16(12):883-94. doi: 10.1111/j.1365-2893.2009.01144.x. Epub 2009 Jun 28.

    PMID: 19566789BACKGROUND

  • Wedemeyer H, Yurdaydin C, Dalekos GN, Erhardt A, Cakaloglu Y, Degertekin H, Gurel S, Zeuzem S, Zachou K, Bozkaya H, Koch A, Bock T, Dienes HP, Manns MP; HIDIT Study Group. Peginterferon plus adefovir versus either drug alone for hepatitis delta. N Engl J Med. 2011 Jan 27;364(4):322-31. doi: 10.1056/NEJMoa0912696.

    PMID: 21268724BACKGROUND

  • Heidrich B, Yurdaydin C, Kabacam G, Ratsch BA, Zachou K, Bremer B, Dalekos GN, Erhardt A, Tabak F, Yalcin K, Gurel S, Zeuzem S, Cornberg M, Bock CT, Manns MP, Wedemeyer H; HIDIT-1 Study Group. Late HDV RNA relapse after peginterferon alpha-based therapy of chronic hepatitis delta. Hepatology. 2014 Jul;60(1):87-97. doi: 10.1002/hep.27102.

    PMID: 24585488BACKGROUND

  • Yurdaydin C, Kahlhofer J, Caruntu FA, Yalcin K, Gurel S, Akarca US, Sprinzl K, Bock HH, Bockmann JH, Papatheodoridis GV, Merle U, Demir M, Hardtke S, Keskin O, Idilman R, Cornberg M, Wedemeyer H, Wranke A. Ten-Year Follow-Up After 96 Weeks Treatment With Peginterferon Plus Tenofovir in Hepatitis D (HIDIT-II): Improved Clinical Outcome After Combination Therapy. United European Gastroenterol J. 2026 Feb;14(1):e70153. doi: 10.1002/ueg2.70153. Epub 2025 Nov 29.

    PMID: 41317314DERIVED

  • Hardtke S, Yurdaydin C, Caruntu FA, Curescu MG, Yalcin K, Akarca US, Gurel S, Zeuzem S, Erhardt A, Luth S, Papatheodoridis GV, Port K, Manns MP, Cornberg M, Kahlhofer J, Wedemeyer H. Frequency, Severity and Impact of Pegylated Interferon Alpha-Associated Flares in Hepatitis D Infection. J Viral Hepat. 2025 Apr;32(4):e70022. doi: 10.1111/jvh.70022.

    PMID: 40087915DERIVED

  • Anastasiou OE, Caruntu FA, Curescu MG, Yalcin K, Akarca US, Gurel S, Zeuzem S, Erhardt A, Luth S, Papatheodoridis GV, Keskin O, Port K, Radu M, Celen MK, Idilman R, Heidrich B, Mederacke I, von der Leyen H, Kahlhofer J, von Karpowitz M, Hardtke S, Cornberg M, Yurdaydin C, Wedemeyer H. Five-year follow-up of 96 weeks peginterferon plus tenofovir disoproxil fumarate in hepatitis D. Liver Int. 2024 Jan;44(1):139-147. doi: 10.1111/liv.15745. Epub 2023 Oct 3.

    PMID: 37787009DERIVED

  • Wedemeyer H, Yurdaydin C, Hardtke S, Caruntu FA, Curescu MG, Yalcin K, Akarca US, Gurel S, Zeuzem S, Erhardt A, Luth S, Papatheodoridis GV, Keskin O, Port K, Radu M, Celen MK, Idilman R, Weber K, Stift J, Wittkop U, Heidrich B, Mederacke I, von der Leyen H, Dienes HP, Cornberg M, Koch A, Manns MP; HIDIT-II study team. Peginterferon alfa-2a plus tenofovir disoproxil fumarate for hepatitis D (HIDIT-II): a randomised, placebo controlled, phase 2 trial. Lancet Infect Dis. 2019 Mar;19(3):275-286. doi: 10.1016/S1473-3099(18)30663-7.

    PMID: 30833068DERIVED

  • Bremer B, Anastasiou OE, Ciesek S, Wedemeyer H. Automated nucleic acid isolation methods for HDV viral load quantification can lead to viral load underestimation. Antivir Ther. 2019;24(2):117-123. doi: 10.3851/IMP3281.

    PMID: 30516520DERIVED

Related Links

MeSH Terms

Conditions

Hepatitis D

Interventions

peginterferon alfa-2aTenofovir

Condition Hierarchy (Ancestors)

Hepatitis, Viral, HumanVirus DiseasesInfectionsRNA Virus InfectionsHepatitisLiver DiseasesDigestive System Diseases

Intervention Hierarchy (Ancestors)

OrganophosphonatesOrganophosphorus CompoundsOrganic ChemicalsAdeninePurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Michael P. Manns, Prof. Dr.

    Hannover Medical School

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NETWORK
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 3, 2009

First Posted

July 7, 2009

Study Start

June 1, 2009

Primary Completion

August 1, 2017

Study Completion

August 2, 2017

Last Updated

January 29, 2018

Record last verified: 2018-01

Locations

GR(1)RO(2)DE(7)